Objective: To study the effects of simvastatin on the lipid metabolism of urine samples in mice by metabolomics. Methods: Urine samples from mice exposed to different doses of simvastatin were collected. The samples were analyzed by ultra-performance liquid chromatography/high resolution time-of-flight mass spectrometry （UPLC/Q-TOF MS） using Acquity BEH C18 column,water-acetonitrile gradient eluted mobile phase, electrospray ion source and negative ion mode. The Markerlynxs software was used for collecting peak information of total ion chromatograms. The acquired data was processed by principal component analysis and orthogonal partial least squares-discriminant analysis. After screening for candidate differential metabolites,the structure of the differential metabolites was identified by the information of MS and MS/MS spectra. Results: After the administration of simvastatin,there was a difference in the rate of weight gain between female and male mice. And their metabolites also showed variation tendency. Six differential lipid species were identified,including palmitic acid,cholestane-pentol,oxo-androstenrone-glucuronide,cholesteryl nitrolinoleate,phosphatidic acid, and phosphatidylethanolamine,showing the changes of lipid metabolism and different patterns of variation in male and female individuals. Conclusion: The results suggest that the clinical use of simvastatin requires the consideration of gender differences.
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